N-(4-fluorobenzyl)-1-hydroxy-6-thioxo-1,6-dihydropyridine-2-carboxamide | 1125465-96-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-(4-fluorobenzyl)-1-hydroxy-6-thioxo-1,6-dihydropyridine-2-carboxamide
• 英文别名: N-[(4-fluorophenyl)methyl]-1-hydroxy-6-sulfanylidene-1,6-dihydropyridine-2-carboxamide；N-[(4-fluorophenyl)methyl]-1-hydroxy-6-sulfanylidenepyridine-2-carboxamide
• CAS: 1125465-96-4
• 化学式: C₁₃H₁₁FN₂O₂S
• 分子量: 278.307
• InChiKey: KWOBZMIOWBOAQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  84.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-羟基-6-硫代-1,6-二氢吡啶-2-羧酸 、 对氟苄胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以95%的产率得到N-(4-fluorobenzyl)-1-hydroxy-6-thioxo-1,6-dihydropyridine-2-carboxamide
  参考文献：
  名称：

  Thioamide Hydroxypyrothiones Supersede Amide Hydroxypyrothiones in Potency against Anthrax Lethal Factor

  摘要：

  Anthrax lethal factor (LF) is a critical virulence factor in the pathogenesis of anthrax. A structure-activity relationship (SAR) of potential lethal factor inhibitors (LFi) is presented in which the zinc-binding group (ZBG), linker, and backbone moieties for a series of hydroxypyrone-based compounds were systematically varied. It was found that hydroxypyrothione ZBGs generate more potent inhibitors than hydroxypyrone ZBGs. Furthermore, coupling the hydroxypyrothione to a backbone group via a thioamide bond improves potency when compared to an amide linker. QM/MM studies show that the thioamide bond in these inhibitors allows for the formation of two additional hydrogen bonds with the protein active site. In both types of hydroxypyrothione compounds, ligand efficiencies of 0.29-0.54 kcal mol(-1) per heavy atom were achieved. The results highlight the need for a better understanding to optimize the interplay between the ZBG, linker, and backbone to get improved LFi.

  DOI：

  10.1021/jm8013212

文献信息

• Thioamide Hydroxypyrothiones Supersede Amide Hydroxypyrothiones in Potency against Anthrax Lethal Factor
  作者：Arpita Agrawal、César Augusto F. de Oliveira、Yuhui Cheng、Jennifer A. Jacobsen、J. Andrew McCammon、Seth M. Cohen

  DOI：10.1021/jm8013212

  日期：2009.2.26

  Anthrax lethal factor (LF) is a critical virulence factor in the pathogenesis of anthrax. A structure-activity relationship (SAR) of potential lethal factor inhibitors (LFi) is presented in which the zinc-binding group (ZBG), linker, and backbone moieties for a series of hydroxypyrone-based compounds were systematically varied. It was found that hydroxypyrothione ZBGs generate more potent inhibitors than hydroxypyrone ZBGs. Furthermore, coupling the hydroxypyrothione to a backbone group via a thioamide bond improves potency when compared to an amide linker. QM/MM studies show that the thioamide bond in these inhibitors allows for the formation of two additional hydrogen bonds with the protein active site. In both types of hydroxypyrothione compounds, ligand efficiencies of 0.29-0.54 kcal mol(-1) per heavy atom were achieved. The results highlight the need for a better understanding to optimize the interplay between the ZBG, linker, and backbone to get improved LFi.